The present invention relates to indicator-dilution (or diffusion) principles of circulatory physiology. More specifically, the invention relates to a method of utilizing nonradioactive markers for measuring lung vascular function and transcapillary transport by optical methods and blood drawn from the systemic arterial system. The relative concentrations of the markers can be readily observed from their infrared and visible spectra in blood which will offer the immediate determination and display of parameters which characterize the lung vascular barrier and will be helpful in assessing lung diseases, such as adult respiratory distress syndrome (ARDS).
Indicator dilution methods based on green dye and other materials capable of absorbing visible light are well established for the measurement of cardiac output and oxygen content. Recently, these methods have been extended to the infrared spectrum by Basset et al. (1981) J. Appl. Physiol. 50:1367-1371 and Neufeld et al. (1983) Proceedings 2nd Int. Symposium on Computing in Anesthesia in Intensive Care, Rotterdam. These devices for measuring light transmittance of indocyanine green dye and deuterated water (D.sub.2 O) have been connected to microcomputers which calculate mean transit times, pulmonary blood flow and extravascular lung water from lung vascular indicator curves. Blood is withdrawn through an optical window and the transmittance of filtered light is detected electronically. This method relies on the high absorbance of (D.sub.2 O) to provide a sensitive and specific indicator of extravascular lung water. The method may be superior to clinical applications of the thermal green dye method of Lewis et al. (1982) Ann. N. Y. Acad. Sci. 384:394-410 in that it does not require an indwelling arterial probe. However, none of these methods can readily obtain microvascular permeability surface area (PS) measurements.
Other methods for evaluation of the microvascular properties of the lung include the multiple radioactive isotope method using .sup.125 I-albumin, .sup.51 Cr-red blood cells .sup.14 C-urea and .sup.3 H-water. See Harris, et al. (1982) Ann. N.Y. Acad. Sci. 384:417-431 and Harris et al. (1987) Respiration Physiology: A Quantitative Approach, Chang and Pavia, editors, Dekker, New York, in press. This method has great advantages in its measurement accuracy; however, it has the disadvantage of analytical complexity and requires the use of radioactive materials.
As discussed in the previously cited works, Harris et al. have shown that .sup.14 C-urea is useful in the measurement of lung vascular PS. However, this radioactive substance cannot be measured by optical means. Harris et al. J. Appl. Physiol. (1987) 62:1852-1859, 1987 have shown that propanediol is virtually identical to urea in its ability to measure alterations in P. S. Galloway et al. (1986) Proc. 39th Ann. Conf. of the Engineering Medicine and Biology Society, 28:157 have shown that the infrared spectral signature of propanediol was such that it could be easily measured in trace quantities in whole blood.